CTP-Defined Large Core Is a Better Predictor of Poor Outcome for Endovascular Treatment Than ASPECTS-Defined Large Core.

BACKGROUND: Recent trials confirmed the effectiveness of endovascular therapy in patients with large ischemic cores. Yet the optimal neuroimaging modalities to define large core remains unclear. We tried to address this question by comparing the functional outcomes in patients receiving thrombectomy selected by either noncontrast computed tomography Alberta Stroke Program Early Computed Tomography Score (ASPECTS) or computed tomography perfusion (CTP). METHODS: This study retrospectively selected patients enrolled in the International Stroke Perfusion Registry between August 2011 and April 2022. Patients with acute stroke with large vessel occlusion in anterior circulation treated with endovascular therapy were included. All received both CTP and noncontrast computed tomography. The primary outcome was defined as poor functional outcome represented by a modified Rankin Scale score of 5 to 6 at 3 months. Large cores were defined in terms of either (1) noncontrast computed tomography ASPECTS ≤5 or (2) core volume ≥70 mL on CTP. RESULTS: A total of 1115 patients were included in the analysis, of which 90 patients had ASPECTS ≤5 (8.1%) and 97 patients CTP core ≥70 mL (8.7%). A fair agreement between ASPECTS and CTP with a κ value of 0.31 (0.21-0.40) was found. Compared with patients with neither CTP nor ASPECTS large cores, those with only ASPECTS-defined large cores (ie, ASPECTS ≤5; n=56) did not have a higher adjusted odds of poor outcome (29%; odds ratio, 1.84 [0.91-3.73]; P=0.089). However, patients with CTP large core but not ASPECTS-defined large core (n=63) had a higher adjusted odds of poor outcome (60%; odds ratio, 3.91 [2.01-7.60]; P<0.001). In time-stratified subgroup analysis (>6 versus ≤6 hours), ASPECTS showed no discriminative difference between ≤5 and >5 in poor outcome for patients receiving endovascular therapy within 6 hours. CONCLUSIONS: CTP core ≥70 mL-defined large cores are more predictive of poor outcome than ASPECTS ≤5-defined core in endovascular therapy patients, particularly within 6 hours after stroke onset.

Endovascular Thrombectomy Versus Medical Management in Isolated M2 Occlusions: Pooled Patient-Level Analysis from the EXTEND-IA Trials, INSPIRE, and SELECT Studies.

OBJECTIVE: The objective of this study was to evaluate functional and safety outcomes of endovascular thrombectomy (EVT) versus medical management (MM) in patients with M2 occlusion and examine their association with perfusion imaging mismatch and stroke severity. METHODS: In a pooled, patient-level analysis of 3 randomized controlled trials (EXTEND-IA, EXTEND-and IA-TNK parts 1 and 2) and 2 prospective nonrandomized studies (INSPIRE and SELECT), we evaluated EVT association with 90-day functional independence (modified Rankin Scale [mRS] = 0-2) in isolated M2 occlusions as compared to medical management overall and in subgroups by mismatch profile status and stroke severity. RESULTS: We included 517 patients (EVT = 195 and MM = 322), baseline median (interquartile range [IQR]) National Institutes of Health Stroke Scale (NIHSS) was 13 (8-19) in EVT versus 10 (6-15) in MM, p < 0.001. Pretreatment ischemic core did not differ (EVT = 10 [0-24] ml vs MM = 9 [3-21] ml, p = 0.59). Compared to MM, EVT was more frequently associated with functional independence (68.3 vs 61.6%, adjusted odds ratio [aOR] = 2.42, 95% confidence interval [CI] = 1.25-4.67, p = 0.008, inverse probability of treatment weights [IPTW]-OR = 1.75, 95% CI = 1.00-3.75, p = 0.05) with a shift toward better mRS outcomes (adjusted cOR = 2.02, 95% CI:1.23-3.29, p = 0.005), and lower mortality (5 vs 10%, aOR = 0.32, 95% CI = 0.12-0.87, p = 0.025). EVT was associated with higher functional independence in patients with a perfusion mismatch profile (EVT = 70.7% vs MM = 61.3%, aOR = 2.29, 95% CI = 1.09-4.79, p = 0.029, IPTW-OR = 2.02, 1.08-3.78, p = 0.029), whereas no difference was found in those without mismatch (EVT = 43.8% vs MM = 62.7%, p = 0.17, IPTW-OR: 0.71, 95% CI = 0.18-2.78, p = 0.62). Functional independence was more frequent with EVT in patients with moderate or severe strokes, as defined by baseline NIHSS above any thresholds from 6 to 10, whereas there was no difference between groups with milder strokes below these thresholds. INTERPRETATION: In patients with M2 occlusion, EVT was associated with improved clinical outcomes when compared to MM. This association was primarily observed in patients with a mismatch profile and those with higher stroke severity. ANN NEUROL 2022;91:629-639.

Modelling the Long-Term Health Outcome and Costs of Thrombectomy in Treating Stroke Patients with Large Ischaemic Core: Comparison between Clinical Trials and Real-World Data.

INTRODUCTION: We aimed to assess the long-term health outcomes and costs of endovascular thrombectomy (EVT) using clinical trials and real-world evidence in patients with large ischaemic core. METHODS: Both clinical trials and the INternational Stroke Perfusion Imaging REgistry (INSPIRE) were used. Patients with acute computed tomography perfusion scan with an ischaemic core of ≥70 mL were included. A Markov model was constructed to simulate the long-term costs and health outcomes (quality-adjusted life year) post-index stroke. Effectiveness of EVT (modified Rankin scale score at 3 months) was derived from the trials and INSPIRE registry (compared to matched patients not treated with EVT), respectively. RESULTS: Based on the trial and real-world data, the overall results revealed varied health benefits and costs due to EVT, with reduced health benefits and increased costs from EVT treatment in everyday practice. The long-term simulation estimated that offering EVT to large vessel occlusion stroke patients with large ischaemic core was associated with greater benefits (1.12 vs. 0.25 quality-adjusted life year gains) and lower (-A$19,320) or higher costs (A$11,278), using trial and real-world data, respectively. The incremental cost of the EVT procedure (i.e., A$14,356) could be primarily offset to a different extent by the reduction in costs related to the nursing home care (-$31,986 vs. -A$1,874) in the clinical trial and real-world practice. CONCLUSIONS: Our results highlight the potential gaps when implementing an effective intervention in the real world and the importance of the rigorous selection of large infarct core patients for EVT.

Cost-Effectiveness of Endovascular Thrombectomy in M2 Occlusion Stroke: Real-World Experience Versus Clinical Trials.

OBJECTIVES: This study sought to establish the cost-effectiveness of endovascular thrombectomy (EVT) in M2 occlusions compared with patients who did not have EVT using both real-world and clinical trial evidence. METHODS: The effectiveness of EVT in M2 occlusions was informed by the International Stroke Perfusion Imaging Registry (INSPIRE, real-world data for a wide range of strokes) and HERMES collaboration, trial data. Patients who received EVT and non-EVT treatment from INSPIRE were matched according to baseline characteristics. A Markov model with 7 health states defined by the 3-month modified Rankin scale (mRS) was constructed. Endovascular thrombectomy and non-EVT-treated patients in real-world, and clinical trials were run through the Markov model separately to generate the results from a limited societal perspective. National statistics and published literature informed the long-term probability of recurrent stroke, mortality, costs of management post-stroke, non-medical care, and nursing home care. RESULTS: A total of 83 (42 EVT and 41 non-EVT) patients were matched of 278 (45 EVT and 233 non-EVT) patients in INSPIRE who had M2 occlusion stroke at presentation. The long-term simulation estimated that offering EVT to M2 occlusion stroke patients was associated with greater benefits (5.48 EVT vs 5.24 non-EVT quality-adjusted life year [QALY]) and higher costs (A$133 457 EVT vs A$126 127 non-EVT) compared with non-EVT treatment in real-world from a limited societal perspective. The incremental cost-effectiveness ratio (ICER) of EVT in real-world was A$29 981 (€19 488)/QALY. The analysis using the data from HERMES collaboration yielded consistent results for the EVT patients. Comparison with real-world cost-effectiveness analyses of EVT in internal carotid artery/middle cerebral artery-M1 (ICA/MCA-M1) occlusion suggested a potential reduced QALY gains and increased ICER in M2 occlusions. CONCLUSIONS: Our study suggested that the benefits gained from EVT in M2 occlusion stroke in the real-world were similar to that derived from the clinical trials. The clinical and cost benefits from EVT appeared to be reduced in M2 compared with that from the ICA/MCA-M1 occlusions. CLINICAL IMPACT: Our study has provided valuable insights into the clinical significance of endovascular therapy (EVT) in the context of M2 occlusion stroke within a real-world setting. It is noteworthy that our findings indicate that the benefits obtained from EVT in M2 occlusion stroke closely align with those observed in controlled clinical trials. However, it is essential to recognize that there is a reduction in the clinical and cost-related advantages when comparing M2 occlusions to more proximal ICA/MCA-M1 occlusions.

Evaluation of a multicomponent intervention to shorten thrombolytic door-to-needle time in stroke patients in China (MISSION): A cluster-randomized controlled trial.

BACKGROUND: Rapid intravenous thrombolysis (IVT) for acute ischemic stroke (AIS) is crucial for improving outcomes. However, few randomized trials of interventions aimed at reducing in-hospital delay have been carried out in China. We aimed to evaluate the effect of a multicomponent intervention on thrombolytic door-to-needle time (DNT) of AIS patients via video teleconference based on the Behavior Change Wheel (BCW) method. METHODS AND FINDINGS: This cluster-randomized trial, conducted between January 1, 2019 and December 31, 2019, randomly allocated 22 hospitals equally to PEITEM (Persuasion Environment reconstruction Incentivization Training Education Modeling) intervention or routine care plus stroke registry and subsequently enrolled 1,634 AIS patients receiving IVT within 4.5 hours upon stroke onset from participant hospitals. The PEITEM group received a 1-year PEITEM 6-component intervention based on the behavioral theory monthly via video teleconference. The primary outcome was the proportion of patients with a DNT of 60 minutes or less. A total of 987 patients participated in the PEITEM group (mean age, 69 years; female, 411 [41.6%]) and 647 patients in the control group (mean age, 70 years; female, 238 [36.8%]). Of all participants, the proportion of DNT ≤60 minutes in the PEITEM group was higher than in the control group (82.0% versus 73.3%; adjusted odds ratio, 1.77; 95% confidence interval (CI), 1.17 to 2.70; ICC, 0.04; P = 0.007). Among secondary outcomes, the average DNT was 43 minutes in the PEITEM group and 50 minutes in the control group (adjusted mean difference: -8.83; 95% CI, -14.03 to -3.64; ICC, 0.12; P = 0.001). Favorable functional outcome (score of 0 to 1 on the modified Rankin scale (mRS)) was achieved in 55.6% patients of the PEITEM group and 50.4% of the control group (adjusted odds ratio, 1.38; 95% CI, 1.00 to 1.90; ICC, 0.01; P = 0.049). Main study limitations include non-blinding of clinicians, and that specific interventions component responsible for the observed changes could not be determined. CONCLUSIONS: The teleconference-delivered PEITEM intervention resulted in a moderate but clinically relevant shorter DNT and better functional outcome in AIS patients receiving IVT. TRIAL REGISTRATION: Clinicaltrials.gov NCT03317639.

A Multicentre Study Comparing Cerebrovascular Disease Profiles in Pacific Islander and Caucasian Populations Presenting with Stroke and Transient Ischaemic Attack.

INTRODUCTION: In a multicentre study, we contrasted cerebrovascular disease profiles in Pacific Island (PI)-born patients (Indigenous Polynesian [IP] or Indo-Fijian [IF]) presenting with transient ischaemic attack (TIA), ischaemic stroke (IS) or intracerebral haemorrhage (ICH) with those of Caucasians (CSs). METHODS: Using a retrospective case-control design, we compared PI-born patients with age- and gender-matched CS controls. Consecutive patients were admitted to 3 centres in South Western Sydney (July 2013-June 2020). Demographic and clinical data studied included vascular risk factors, stroke subtypes, and imaging characteristics. RESULTS: There were 340 CS, 183 (27%) IP, and 157 (23%) IF patients; mean age 65 years; and 302 (44.4%) female. Of these, 587 and patients presented with TIA/IS and 93 (13.6%) had ICH. Both IP and IF patients were significantly more likely to present >24 h from symptom onset (odds ratios [ORs] vs. CS 1.87 and 2.23). IP patients more commonly had body mass indexes >30 (OR 1.94). Current smoking and excess alcohol intake were higher in CS. Hypertension, diabetes, and chronic kidney disease were significantly higher in both IP and IF groups in comparison to CS. IP patients had higher rates of AF and those with known AF were more commonly undertreated than both IF and CS patients (OR 2.24, p = 0.007). ICH was more common in IP patients (OR 2.32, p = 0.005), while more IF patients had intracranial arterial disease (OR 5.10, p < 0.001). DISCUSSION/CONCLUSION: Distinct cerebrovascular disease profiles are identifiable in PI-born patients who present with TIA or stroke symptoms in Australia. These may be used in the future to direct targeted approaches to stroke prevention and care in culturally and linguistically diverse populations.

Cerebrovascular Disease Profiles of Culturally and Linguistically Diverse Communities in South Western Sydney and New South Wales.

INTRODUCTION: Culturally and linguistically diverse (CALD) communities are growing globally. Understanding patterns of cerebrovascular disease in CALD communities may improve health outcomes through culturally specific interventions. We compared rates of transient ischaemic attack (TIA)/stroke (ischaemic stroke, intracerebral haemorrhage) and stroke risk factor prevalence in overseas and Australian-born people in South Western Sydney (SWS) and New South Wales (NSW). METHODS: This was a 10-year retrospective analysis (2011-2020) of SWS and NSW age-standardized rates per 100,000 person-years of TIA/stroke. Data were extracted from Health Information Exchange and Secure Analytics for Population Health Research and Intelligence systems. Rates of hypertension, type 2 diabetes mellitus (T2DM), atrial fibrillation (AF), smoking, and obesity were also calculated. RESULTS: The SWS and NSW age-standardized rate of TIA/stroke for people born in Australia was 100 per 100,000 person-years (100/100,000/year). In SWS, 56.6% of people were overseas-born compared to 29.8% for NSW. The age-standardized rate of TIA/stroke for Polynesian-born people was more than double that of Australian-born people (p < 0.001). Hypertension (33 [SWS] vs. 27/100,000/year [NSW]) and T2DM (36 [SWS] vs. 26/100,000/year [NSW]) were the most common risk factors with rates >50/100,000/year (hypertension) and >80/100,000/year (T2DM) for people born in Polynesia, Melanesia, and Central America. Rates of T2DM, AF, and obesity for Polynesian-born people were over threefold greater than people born in Australia. DISCUSSION/CONCLUSION: Greater rates of TIA/stroke were observed in specific CALD communities, with increased rates of cerebrovascular risk factors. Culturally specific, targeted interventions may bridge health inequalities in cerebrovascular disease.

Stroke Patients With Faster Core Growth Have Greater Benefit From Endovascular Therapy.

BACKGROUND AND PURPOSE: This study aimed to explore whether the therapeutic benefit of endovascular thrombectomy (EVT) was mediated by core growth rate. METHODS: This retrospective cohort study identified acute ischemic stroke patients with large vessel occlusion and receiving reperfusion treatment, either EVT or intravenous thrombolysis (IVT), within 4.5 hours of stroke onset. Patients were divided into 2 groups: EVT versus IVT only patients (who had no access to EVT). Core growth rate was estimated by the acute core volume on perfusion computed tomography divided by the time from stroke onset to perfusion computed tomography. The primary clinical outcome was good outcome defined by 3-month modified Rankin Scale score of 0-2. Tissue outcome was the final infarction volume. RESULTS: A total of 806 patients were included, 429 in the EVT group (recanalization rate of 61.6%) and 377 in the IVT only group (recanalization rate of 44.7%). The treatment effect of EVT versus IVT only was mediated by core growth rate, showing a significant interaction between EVT treatment and core growth rate in predicting good clinical outcome (interaction odds ratio=1.03 [1.01-1.05], P=0.007) and final infarct volume (interaction odds ratio=-0.44 [-0.87 to -0.01], P=0.047). For patients with fast core growth of >25 mL/h, EVT treatment (compared with IVT only) increased the odds of good clinical outcome (adjusted odds ratio=3.62 [1.21-10.76], P=0.021) and resulted in smaller final infarction volume (37.5 versus 73.9 mL, P=0.012). For patients with slow core growth of <15 mL/h, there were no significant differences between the EVT and the IVT only group in either good clinical outcome (adjusted odds ratio=1.44 [0.97-2.14], P=0.070) or final infarction volume (22.6 versus 21.9 mL, P=0.551). CONCLUSIONS: Fast core growth was associated with greater benefit from EVT compared with IVT in the early <4.5-hour time window.

Permeability Measures Predict Hemorrhagic Transformation after Ischemic Stroke.

OBJECTIVE: We sought to examine the diagnostic utility of existing predictors of any hemorrhagic transformation (HT) and compare them with new perfusion imaging permeability measures in ischemic stroke patients receiving alteplase only. METHODS: A pixel-based analysis of pretreatment CT perfusion (CTP) was undertaken to define the optimal CTP permeability thresholds to predict the likelihood of HT. We then compared previously proposed predictors of HT using regression analyses and receiver operating characteristic curve analysis to produce an area under the curve (AUC). We compared AUCs using χ2 analysis. RESULTS: From 5 centers, 1,407 patients were included in this study; of these, 282 had HT. The cohort was split into a derivation cohort (1,025, 70% patients) and a validation cohort (382 patients or 30%). The extraction fraction (E) permeability map at a threshold of 30% relative to contralateral had the highest AUC at predicting any HT (derivation AUC 0.85, 95% confidence interval [CI], 0.79-0.91; validation AUC 0.84, 95% CI 0.77-0.91). The AUC improved when permeability was assessed within the acute perfusion lesion for the E maps at a threshold of 30% (derivation AUC 0.91, 95% CI 0.86-0.95; validation AUC 0.89, 95% CI 0.86-0.95). Previously proposed associations with HT and parenchymal hematoma showed lower AUC values than the permeability measure. INTERPRETATION: In this large multicenter study, we have validated a highly accurate measure of HT prediction. This measure might be useful in clinical practice to predict hemorrhagic transformation in ischemic stroke patients before receiving alteplase alone. ANN NEUROL 2020;88:466-476.

Intraarterial Versus Intravenous Tirofiban as an Adjunct to Endovascular Thrombectomy for Acute Ischemic Stroke.

BACKGROUND AND PURPOSE: This study aimed to evaluate the treatment effect of intraarterial versus intravenous tirofiban during endovascular thrombectomy in acute ischemic stroke. METHODS: This study retrospectively examined 503 patients with acute ischemic stroke with large vessel occlusion who received endovascular thrombectomy within 24 hours of stroke onset. Patients were divided into 3 groups: no tirofiban (n=354), intraarterial tirofiban (n=79), and intravenous tirofiban (n=70). The 3 groups were compared in terms of recanalization rate, symptomatic intracerebral hemorrhage, in-hospital death rate, 3-month death, and 3-month outcomes measured by modified Rankin Scale score (good clinical outcome of 0-2, poor outcome of 5-6). The comparison was statistically assessed by propensity score matching, followed by Freidman rank-sum test and pairwise Wilcoxon signed-rank test with Bonferroni correction. RESULTS: The propensity score matching resulted in 92 matched triplets. Compared with the no-tirofiban group, the intravenous tirofiban group showed significantly increased recanalization (96.7% versus 64.1%, P<0.001), an increased rate of 3-month good outcome (69.5% versus 51.2%, P=0.034), and a lower rate of 3-month poor outcome (12.2% versus 41.4%, P<0.001). There was no significant difference between the tirofiban intravenous and no-tirofiban groups in terms of symptomatic intracerebral hemorrhage (2.2% versus 0%, P=1.000). However, symptomatic intracerebral hemorrhage was significantly increased in the intraarterial-tirofiban group compared with the no-tirofiban group (19.1% versus 0%, P<0.001), with an increased rate of in-hospital death (23.6% versus 0% P<0.001), and increased rate of 3-month death (26.8% versus 11.1%, P=0.021). The intraarterial-tirofiban and no-tirofiban group showed no significant difference in recanalization rate (66.3% versus 64.1%, P=1.000). CONCLUSIONS: As an adjunct to endovascular thrombectomy, intravenous tirofiban is associated with high recanalization rate and good outcome, whereas intraarterial tirofiban is associated with high hemorrhagic rate and death rate.

Perfusion Computed Tomography Accurately Quantifies Collateral Flow After Acute Ischemic Stroke.

Background and Purpose- This study aimed to derive and validate an optimal collateral measurement on computed tomographic perfusion imaging for patients with acute ischemic stroke. Methods- In step 1 analysis of 22 patients, the parasagittal region of the ischemic hemisphere was divided into 6 pial arterial zones to derive the optimal collateral threshold by receiver operating characteristic analysis. The collateral threshold was then used to define the collateral index in step 2. In step 2 analysis of 156 patients, the computed tomographic perfusion collateral index was compared with collateral scores on dynamic computed tomographic angiography in predicting good clinical outcome by simple regression. Results- The optimal collateral threshold was delay time >6 s (sensitivity, 88%; specificity, 92%). The computed tomographic perfusion collateral index, defined by the ratio of delay time >6 s/delay time >2 s volume, showed a significant correlation with dynamic computed tomographic angiography collateral scores (correlation coefficient, 0.62; P<0.001), with an optimal cut point of 31.8% in predicting good collateral status (sensitivity of 83% and specificity of 86%). When predicting good clinical outcome, the delay time collateral index showed a similar predictive power to dynamic computed tomographic angiography collaterals (area under the curve, 0.78 [0.67-0.83] and 0.77 [0.69-0.84], respectively; P<0.001). Conclusions- Computed tomographic perfusion can accurately quantify collateral flow after acute ischemic stroke.

The blood pressure paradox in acute ischemic stroke.

OBJECTIVE: To explore the association of poststroke baseline blood pressure with cerebral collateral flow and functional outcome in acute ischemic patients with large vessel occlusion/stenosis. METHODS: Patients identified with large vessel occlusion/stenosis with baseline multimodal computed tomography, follow-up imaging, and complete clinical profiles were included. A 90-day modified Rankin Scale of 0-1 was defined as an excellent functional outcome. Cerebral collateral flow was quantified by the volume ratio of tissue within the delay time >3 seconds perfusion lesion with severely delayed contrast transit (delay time >3 seconds/delay time >6 seconds). RESULTS: There were 306 patients included in this study. With every increase of 10 mmHg in baseline systolic blood pressure, the odds of achieving an excellent functional outcome decreased by 12% in multivariate analysis (odds ratio = 0.88, p = 0.048). Conversely, increased baseline blood pressure was associated with better collateral flow. In subgroup analysis of patients with major reperfusion, higher blood pressure was associated with decreased infarct growth and a better clinical outcome, and vice versa in patients without reperfusion. INTERPRETATION: Higher baseline blood pressure in acute ischemic stroke patients with large vessel occlusion/stenosis was associated with better collateral flow. However, for patients without reperfusion, higher baseline blood pressure was associated with increased infarct growth, leading to an unfavorable clinical outcome. The relationship between blood pressure and outcomes is highly dependent on reperfusion, and active blood pressure-lowering treatment may be inappropriate in acute ischemic stroke patients prior to reperfusion treatment. ANN NEUROL 2019;85:331-339.

Single-phase CT angiography: collateral grade is independent of scan weighting.

PURPOSE: Collateral grading may vary on single-phase CTA (sCTA) depending on whether the CTA is arterial (A), arteriovenous (AV), or venous (V) weighted. We studied the impact of sCTA weighting on collateral grading using the Tan, MAAS, and Menon methods, and their ability to predict infarct and clinical outcome hypothesizing that AV-weighted sCTA should better predict these outcomes. METHODS: Multicenter retrospective analysis of 212 patients undergoing baseline CTP/sCTA. sCTA weighting was determined by comparing ICA to torcula AV ratios with those from concomitant CTP time-density curves at peak arterial or venous contrast attenuation. A generalized linear mixed model investigated the predictive value for infarct volume or 90-day mRS of the three collateral scores stratified by sCTA weighting and adjusting for age, sex, clot burden score (CBS), and NIHSS. Bayesian information criterion (BIC) differences were calculated between the null and fitted models. RESULTS: Mean age, baseline median NIHSS, ASPECTS, and onset to treatment time were 69.89 ± 14.45, 13 (6-18), 10 (8-10), and 128 (66-181) minutes. sCTA scans were AV-weighted in 137/212 (65%) and A-weighted in 73 (34%). No association was demonstrated between sCTA weighting, hospital site, and sCTA technique. All collateral scores were related to infarct volume irrespective of sCTA weighting, with greatest fit with the regional leptomeningeal score (BIC 18.29, p = 0.0001). No association was shown between sCTA weighting, collateral grade, and clinical outcome. CONCLUSION: sCTA weighting did not significantly impact collateral grade using three common collateral scores or their ability to predict final infarct.

Endovascular Thrombectomy.

Background and Purpose- This study aimed to explore safety of tirofiban in endovascular treatment of acute ischemic stroke. Methods- Two hundred eighteen ischemic stroke patients receiving endovascular thrombectomy were prospectively recruited, with 94 treated with intra-arterial tirofiban and 124 were not. The 2 groups were compared in terms of symptomatic intracranial hemorrhage (ICH) and fatal ICH rate by the χ2 test and logistic regression. Results- Patients treated with tirofiban compared with those without tirofiban had significantly higher rate of symptomatic ICH (14.6% versus 5.7%; P=0.027) and fatal ICH (8.8% versus 1.6%; P=0.014). Tirofiban-treated patients had increased odds of symptomatic ICH by 2.9-fold (95% CI, 1.1-7.5), and odds of fatal ICH increased by 5.9-fold (95% CI, 1.2-28.4). Conclusions- Tirofiban treatment increases risk of major ICH after endovascular thrombectomy for acute ischemic stroke in this nonrandomized study.

Correction for Delay and Dispersion Results in More Accurate Cerebral Blood Flow Ischemic Core Measurement in Acute Stroke.

BACKGROUND AND PURPOSE: This study aimed to assess how the ischemic core measured by perfusion computed tomography (CTP) was affected by the delay and dispersion effect. METHODS: Ischemic stroke patients having CTP performed within 6 hours of onset were included. The CTP data were processed twice, generating standard cerebral blood flow (sCBF) and delay- and dispersion-corrected CBF (ddCBF), respectively. Ischemic core measured by the sCBF and ddCBF was then compared at the relative threshold <30% of normal tissue. Two references for ischemic core were used: acute diffusion-weighted imaging or 24-hour diffusion-weighted imaging in patients with complete recanalization. Difference of core volume between CTP and diffusion-weighted imaging was estimated by Mann-Whitney U test and limits of agreement. Patients were also classified into favorable and unfavorable CTP patterns. The imaging pattern classification by sCBF and ddCBF was compared by the χ2 test; their respective ability to predict good clinical outcome (3-month modified Rankin Scale score) was tested in logistic regression. RESULTS: Fifty-five patients were included in this study. Median sCBF ischemic core volume was 38.5 mL (12.4-61.9 mL), much larger than the median core volume of 17.2 mL measured by ddCBF (interquartile range, 5.5-38.8; P<0.001). Moreover, compared with sCBF <30%, ddCBF <30% measured the ischemic core much closer to diffusion-weighted imaging core references, with the mean volume difference of -0.1 mL (95% limits of agreement, -25.4 to 25.2; P=0.97) and 16.7 mL (95% limits of agreement, -21.7 to 55.2; P<0.001), respectively. Imaging patterns defined by sCBF showed a difference to that defined by ddCBF (P<0.001), with 12 patients classified as favorable imaging patterns by ddCBF but as unfavorable by sCBF. The favorable imaging pattern classified by ddCBF, compared with sCBF classification, had higher predictive power for good clinical outcome (odds ratio, 7.8 [2-30.5] and 3.1 [0.9-11], respectively). CONCLUSIONS: Delay and dispersion correction increases the accuracy of ischemic core measurement on CTP.

Identification of Corticospinal Tract Lesion for Predicting Outcome in Small Perfusion Stroke.

Background and Purpose- Whether patients with small perfusion lesions benefit from thrombolysis remains an uncertainty. We assessed acute ischemic stroke patients with a total perfusion lesion of <15 mL and tested the hypothesis the pattern of corticospinal tract (CST) involvement might predict outcome in thrombolysis-eligible patients. Methods- We used a prospectively collected cohort of acute ischemic stroke patients being assessed for thrombolysis at 7 centers. Three neurologists categorized the presence of hypoperfusion and infarction within CST. Excellent outcome was defined as 90-day modified Rankin Scale score 0 to 1. Results- Of 2654 patients, 407 had a perfusion lesion <15 mL and were clinically eligible for thrombolysis (243 being treated). Median National Institutes of Health Stroke Scale was 5.0, and 312 (76.7%) patients achieved excellent outcome. Alteplase treatment was an independent unfavorable factor for excellent outcome (alteplase-treated 72.0% versus untreated 83.5%; odds ratio, 0.541; P=0.025). For patients with CST hypoperfusion without CST infarction, alteplase treatment was an independent favorable factor for excellent outcome (alteplase-treated 75.6% versus untreated 47.1%; odds ratio, 4.096; P=0.045). Among patients with CST infarction, alteplase treatment was an independent unfavorable factor for excellent outcome (alteplase-treated 30.6% versus untreated 88.9%; odds ratio, 0.002; P=0.003). Among patients without either CST hypoperfusion or CST infarction, alteplase treatment was not an independent influencing factor for excellent outcome (alteplase-treated 80.1% versus untreated 87.7%; P=0.258). Conclusions- Only patients with CST hypoperfusion without CST infarction among eligible acute ischemic stroke patients with small perfusion lesions could benefit from thrombolysis, which needs to be confirmed in future prospective studies. Patient selection, including an assessment of lesion location rather than purely lesion volume, may be ideal.

Ischemic core thresholds change with time to reperfusion: A case control study.

INTRODUCTION: We aimed to identify whether acute ischemic stroke patients with known complete reperfusion after thrombectomy had the same baseline computed tomography perfusion (CTP) ischemic core threshold to predict infarction as thrombolysis patients with complete reperfusion. METHODS: Patients who underwent thrombectomy were matched by age, clinical severity, occlusion location, and baseline perfusion lesion volume to patients who were treated with intravenous alteplase alone from the International Stroke Perfusion Imaging Registry. A pixel-based analysis of coregistered pretreatment CTP and 24-hour diffusion-weighted imaging (DWI) was then undertaken to define the optimum CTP thresholds for the ischemic core. RESULTS: There were 132 eligible thrombectomy patients and 132 matched controls treated with alteplase alone. Baseline National Institutes of Health Stroke Scale (median, 15; interquartile range [IQR], 11-19), age (median, 65; IQR, 59-80), and time to intravenous treatment (median, 153 minutes; IQR, 82-315) were well matched (all p > 0.05). Despite similar baseline CTP ischemic core volumes using the previously validated measure (relative cerebral blood flow [rCBF], <30%), thrombectomy patients had a smaller median 24-hour infarct core of 17.3ml (IQR, 11.3-32.8) versus 24.3ml (IQR, 16.7-42.2; p = 0.011) in alteplase-treated controls. As a result, the optimal threshold to define the ischemic core in thrombectomy patients was rCBF <20% (area under the curve [AUC], 0.89; 95% CI, 0.84, 0.94), whereas in alteplase controls the optimal ischemic core threshold remained rCBF <30% (AUC, 0.83; 95% CI, 0.77, 0.85). INTERPRETATION: Thrombectomy salvaged tissue with lower CBF, likely attributed to earlier reperfusion. For patients who achieve rapid reperfusion, a stricter rCBF threshold to estimate the ischemic core should be considered. Ann Neurol 2017;82:995-1003.

Perfusion computed tomography in patients with stroke thrombolysis.

See Saver (doi:10.1093/awx020) for a scientific commentary on this article.Stroke shortens an individual's disability-free life. We aimed to assess the relative prognostic influence of pre- and post-treatment perfusion computed tomography imaging variables (e.g. ischaemic core and penumbral volumes) compared to standard clinical predictors (such as onset-to-treatment time) on long-term stroke disability in patients undergoing thrombolysis. We used data from a prospectively collected international, multicentre, observational registry of acute ischaemic stroke patients who had perfusion computed tomography and computed tomography angiography before treatment with intravenous alteplase. Baseline perfusion computed tomography and follow-up magnetic resonance imaging were analysed to derive the baseline penumbra volume, baseline ischaemic core volume, and penumbra salvaged from infarction. The primary outcome measure was the effect of imaging and clinical variables on Disability-Adjusted Life Year. Clinical variables were age, sex, National Institutes of Health Stroke Scale score, and onset-to-treatment time. Age, sex, country, and 3-month modified Rankin Scale were extracted from the registry to calculate disability-adjusted life-year due to stroke, such that 1 year of disability-adjusted life-year equates to 1 year of healthy life lost due to stroke. There were 772 patients receiving alteplase therapy. The number of disability-adjusted life-year days lost per 1 ml of baseline ischaemic core volume was 17.5 (95% confidence interval, 13.2-21.9 days, P < 0.001). For every millilitre of penumbra salvaged, 7.2 days of disability-adjusted life-year days were saved (ß = -7.2, 95% confidence interval, -10.4 to -4.1 days, P < 0.001). Each minute of earlier onset-to-treatment time resulted in a saving of 4.4 disability-free days after stroke (1.3-7.5 days, P = 0.006). However, after adjustment for imaging variables, onset-to-treatment time was not significantly associated with savings in disability-adjusted life-year days. Pretreatment perfusion computed tomography can (independently of clinical variables) predict significant gains, or loss, of disability-free life in patients undergoing reperfusion therapy for stroke. The effect of earlier treatment on disability-free life appears explained by salvage of penumbra, particularly when the ischaemic core is not too large.

Influence of Penumbral Reperfusion on Clinical Outcome Depends on Baseline Ischemic Core Volume.

BACKGROUND AND PURPOSE: In alteplase-treated patients with acute ischemic stroke, we investigated the relationship between penumbral reperfusion at 24 hours and clinical outcomes, with and without adjustment for baseline ischemic core volume. METHODS: Data were collected from consecutive acute ischemic stroke patients with baseline and follow-up perfusion imaging presenting to hospital within 4.5 hours of symptom onset at 7 hospitals. Logistic regression models were used for predicting the effect of the reperfused penumbral volume on the dichotomized modified Rankin Scale (mRS) at 90 days and improvement of National Institutes of Health Stroke Scale at 24 hours, both adjusted for baseline ischemic core volume. RESULTS: This study included 1507 patients. Reperfused penumbral volume had moderate ability to predict 90-day mRS 0 to 1 (area under the curve, 0.77; R2, 0.28; P<0.0001). However, after adjusting for baseline ischemic core volume, the reperfused penumbral volume was a strong predictor of good functional outcome (area under the curve, 0.946; R2, 0.55; P<0.0001). For every 1% increase in penumbral reperfusion, the odds of achieving mRS 0 to 1 at day 90 increased by 7.4%. Improvement in acute 24-hour National Institutes of Health Stroke Scale was also significantly related to the degree of reperfused penumbra (R2, 0.31; P<0.0001). This association was again stronger after adjustment for baseline ischemic core volume (R2, 0.41; P<0.0001). For each 1% of penumbra that was reperfused, the 24-hour National Institutes of Health Stroke Scale decreased by 0.069 compared with baseline. CONCLUSIONS: In patients treated with alteplase, the extent of the penumbra that is reperfused is a powerful predictor of early and late clinical outcomes, particularly when baseline ischemic core is taken into account.

Validating a Predictive Model of Acute Advanced Imaging Biomarkers in Ischemic Stroke.

BACKGROUND AND PURPOSE: Advanced imaging to identify tissue pathophysiology may provide more accurate prognostication than the clinical measures used currently in stroke. This study aimed to derive and validate a predictive model for functional outcome based on acute clinical and advanced imaging measures. METHODS: A database of prospectively collected sub-4.5 hour patients with ischemic stroke being assessed for thrombolysis from 5 centers who had computed tomographic perfusion and computed tomographic angiography before a treatment decision was assessed. Individual variable cut points were derived from a classification and regression tree analysis. The optimal cut points for each assessment variable were then used in a backward logic regression to predict modified Rankin scale (mRS) score of 0 to 1 and 5 to 6. The variables remaining in the models were then assessed using a receiver operating characteristic curve analysis. RESULTS: Overall, 1519 patients were included in the study, 635 in the derivation cohort and 884 in the validation cohort. The model was highly accurate at predicting mRS score of 0 to 1 in all patients considered for thrombolysis therapy (area under the curve [AUC] 0.91), those who were treated (AUC 0.88) and those with recanalization (AUC 0.89). Next, the model was highly accurate at predicting mRS score of 5 to 6 in all patients considered for thrombolysis therapy (AUC 0.91), those who were treated (0.89) and those with recanalization (AUC 0.91). The odds ratio of thrombolysed patients who met the model criteria achieving mRS score of 0 to 1 was 17.89 (4.59-36.35, P<0.001) and for mRS score of 5 to 6 was 8.23 (2.57-26.97, P<0.001). CONCLUSIONS: This study has derived and validated a highly accurate model at predicting patient outcome after ischemic stroke.